This invention pertains to the treatment of tumors, more particularly to a method for identifying, localizing, and measuring the dose delivered by brachytherapy seeds using imaging techniques.
Brachytherapy is a form of radiation treatment in which tiny pellets, commonly referred to as seeds, containing a radioactive material such as iodine-125 or palladium-103, are implanted within a tumor-containing tissue or organ. Brachytherapy allows the delivery of high doses of radiation to targeted tissues and organs, while limiting the radiation dose to neighboring normal (non-cancerous) tissues and organs.
Over the last few years, the use of permanent interstitial implants for treating carcinoma of the prostate has sharply increased, especially in early stages of the disease. When using permanent interstitial implants, the delivered dose of radiation and dose distribution within the target and neighboring organs depends on the accuracy of the brachytherapy source positioning. Often, implanted seed positions deviate from the optimal pattern developed in the treatment planning, primarily due to source positioning errors caused by inaccurate needle placement (depth and position), prostate motion, and seed splaying. See P. L. Roberson et al., xe2x80x9cSource placement error for permanent implant of the prostate.xe2x80x9d Medical Physics, vol. 24(2), pp. 251-257 (1997).
Postoperative assessment of patient outcome and dosimetric descriptions of implants have relied on seed localization using computed tomography (CT), fluoroscopic images, magnetic resonance imaging (MRI), ultrasound imaging, or scanned radiographs. See J. Willins et al., xe2x80x9cCT-based Dosimetry for Transperineal I-125 Prostate Brachytherapy,xe2x80x9d Int. J. Radiat. Oncol. Biol. Phy., vol. 39(2), pp.347-53 (1997). Once imaging is complete, seed positioning and orientation are extracted from these images and used for three-dimensional reconstruction of the treatment area. Seed placement errors, doses, and dose volume histograms are determined post-operatively and correlated with pre-implant calculations. However, the resolution of these imaging methods and the resolution of subsequent seed localization are limited to approximately 5 mm. Problems include artifacts in the images, and the difficulties associated with localizing seeds across multiple CT planar images. See W. S. Bice et al., xe2x80x9cSource localization from axial image sets by iterative relaxation of the nearest neighbor criterion.xe2x80x9d Med. Phys., vol. 26(9), pp. 1919-1924 (1999). Furthermore, no existing method can provide implanted seed dosimetry without the prior localization of individual seeds.
Evaluating seed positions and resulting dose distributions is also encumbered by difficulties in target identification, and by volume changes in the implant area after implantation. See Willins et al. (1997). Some algorithms have been developed in the last decade (e.g., orthogonal film reconstruction, iterative relaxation, etc.) to automate seed identification and localization, based on various imaging methods (e.g., CT, fluoroscopic images, ultrasound images, MRI, etc.). However, despite increasingly sophisticated mathematical methods, algorithmic predictions have retained a high level of uncertainty. For example, a phantom study found that orthogonal film reconstruction techniques were able to locate only 66% of seeds within 5 mm of their actual location, while iterative relaxation methods in clinical studies had only a 72% success rate. See Bice et al. (1999).
The uncertainty in localizing low energy photon emitters (e.g., Pd-103), results in an unacceptable error when calculating doses from a brachytherapy seed to targeted or normal tissues. This error arises because the dose rapidly decreases within a few centimeters of the seed. See R. Nath et al., xe2x80x9cDosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy Committee Task Group No.43.xe2x80x9d Med. Phys., vol.22(2), pp.209-234 (1995). For instance, for Pd-103 the dose fall-off along the radial transverse axis of the seed is approximately 25% for each 5 mm distance from the source. By comparison, I-125 has a dose fall-off rate of approximately 10% per 5 mm.
U.S. Pat. No. 6,187,037 describes a pre-calibrated, integral radiation device for vascular implantation that delivers site-specific therapy to prevent restenosis. The device comprises a tubular structure formed of bio-compatible metal that can be activated by irradiation or neutron bombardment, or by a proton or electron beam.
WO 99/33063 describes un-encapsulated palladium-103 brachytherapy sources produced by irradiating pre-formed rhodium metal or rhodium alloy seeds with protons from a charged particle accelerator.
U.S. Pat. No. 6,163,947 and WO 97/19724 describe a brachytherapy device for radiotherapy of interstitial malignant neoplasms or other radiation-treatable diseases. The device comprises a hollow tubular support having a hollow tube-shaped seed-substrate. Radioactive source material is deposited as a layer on the external surface of the device. In one embodiment, the radiation-emitting layer of the device may be prepared by plating the seed-substrate with a suitable non-radioactive isotope that may be transmuted in situ by neutron bombardment.
An unfilled need exists for a cost-effective device and method for improving cancer treatment by increasing the level of accuracy and convenience in dose determinations, and in identifying and localizing brachytherapy seeds.
We have discovered a reliable and inexpensive device and method to improve the dosimetry, identification, and localization of brachytherapy seeds. The novel brachytherapy source may be adapted, for example, to produce positron emissions. In one embodiment, a positron or gamma emitter is embedded as a marker in a brachytherapy seed and is then imaged using external radiation detection devices (e.g., positron emission tomography (PET), single-photon emission computed tomography (SPECT), gamma camera, etc., resulting in a new type of seed definition and localization, and direct dosimetry from the dose-volume data produced by radiological imaging software.
In another embodiment, the novel device and method provides a means for irradiating titanium seed capsules using protons, either before or after encapsulation, to produce V-48, which is a positron emitter. Irradiation after encapsulation also provides a means for producing both Pd-103 and V-48 in one step, avoiding the need for xe2x80x9chot-loading.xe2x80x9d (xe2x80x9cHot-loadingxe2x80x9d is the use of radioactive components during the manufacturing of brachytherapy seeds, which is more difficult and costly than using stable components during initial manufacturing.) Seeds produced with both Pd-103 and V-48 together in one step may have different dosimetric characteristics from those produced with a minute quantity of V-48 prepared separately from Pd-103. Such a situation may result if the contribution of the V-48 isotope to the total dose is non-negligible as compared to the contribution of Pd-103. The method described also provides a means for producing seeds with varying activity of positron emissions.